Methods and compositions for treating brain diseases
The present disclosure provides targeting peptides and vectors containing a sequence that encodes targeting peptides that deliver agents to the brain.
1. A modified adeno-associated virus (AAV) capsid protein comprising a targeting peptide, wherein the targeting peptide is from 3 to 10 amino acids in length and wherein the targeting peptide targets an AAV to brain vascular endothelium, wherein the targeting peptide is GMNAFRA (SEQ ID NO:41), as expressed in an amino to carboxy orientation or in a carboxy to amino orientation.
2. The capsid protein of claim 1 , wherein the targeting peptide targets a diseased brain vascular endothelium.
3. The capsid protein of claim 2 , wherein the target peptide targets brain vascular endothelium in a subject that has a lysosomal storage disease.
4. The capsid protein of claim 2 , wherein the targeting peptide targets TPP1-deficient-brain vascular endothelium.
5. The capsid protein of claim 1 , wherein the AAV is AAV2.
6. An AAV virus containing the capsid protein of claim 1 .
7. A method to deliver an agent to the central nervous system of a subject, comprising administering the virus of claim 6 to the subject.
8. The method of claim 7 , wherein the AAV is AAV2.
9. The AAV virus of claim 6 , wherein the AAV is AAV2.